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Blocking Src, the kinase that lets prostate cancer cells talk to bone-dissolving cells, did nothing when added to chemotherapy.
Src kinase mediates the crosstalk between prostate cancer cells and osteoclasts, and preclinical work suggested that inhibiting it would be synergistic with docetaxel. READY was the test.
It randomised 1,522 men with chemotherapy-naive metastatic castration-resistant prostate cancer to docetaxel and prednisone with dasatinib 100 mg once daily or placebo, blinded to patients, investigators and analysts.
At the final analysis, median follow-up 19.0 months and 914 deaths, median overall survival was 21.5 months (95 percent confidence interval 20.3 to 22.8) with dasatinib and 21.2 months (20.0 to 23.4) with placebo, stratified hazard ratio 0.99 (95.5 percent confidence interval 0.87 to 1.13, p=0.90).
The commonest grade 3 to 4 adverse events with dasatinib against placebo were diarrhoea (58 of 762, 8 percent, against 27 of 760, 4 percent), fatigue (62, 8 percent, against 42, 6 percent) and asthenia (40, 5 percent, against 23, 3 percent). Grade 3 to 4 pleural effusions, the toxicity dasatinib is known for in leukaemia, were uncommon at 10 (1 percent) against three (under 1 percent).
READY belongs with COMET-1, CALGB 90401 and the endothelin trials in the group of bone-microenvironment hypotheses that produced large, well-conducted, completely null trials.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
1,522 randomised.
Confidence interval is 95.5 percent, as reported.
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (median)primary | Docetaxel, prednisone and dasatinib | 762 | 21.5 months | 0.99 (0.87 to 1.13) | 0.90 | link |
| Docetaxel, prednisone and placebo | 760 | 21.2 months |
Shares SWOG S0421, Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC).
Shares COMET-1, Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC).
Shares Prostate cancer programmes that failed, and what each failure taught, Prednisone, Castration-resistant prostate cancer (CRPC), Docetaxel.
Shares SWOG S0421, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Prednisone, Castration-resistant prostate cancer (CRPC).
Shares Prostate cancer programmes that failed, and what each failure taught, Prednisone, Castration-resistant prostate cancer (CRPC), Docetaxel.
Shares SWOG S0421, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer.
Shares Prostate cancer programmes that failed, and what each failure taught, Bone metastases and skeletal-related events, Castration-resistant prostate cancer (CRPC), Bristol Myers Squibb.